S. aureus is a Gram-positive spherical bacterium and is the leading cause of infection of the bloodstream, lower respiratory tract, and skin and other soft tissues. It causes a range of illnesses from minor skin infections to life-threatening diseases including pneumonia and septicaemia, and the mortality associated with S. aureus per annum in the US exceeds that of any other infectious disease, including HIV/AIDS.
There is currently no authorised vaccine against S. aureus. A vaccine based on a mixture of surface polysaccharides from bacterial types 5 and 8, StaphVAX™, failed to reduce infections when compared to the placebo group in a phase III clinical trial in 2005. Reference 1 reports data on the “V710” vaccine from Merck and Intercell which is based on a single antigen, IsdB, a conserved iron-sequestering cell-surface protein [2,3]. However, the clinical trials of V710 were terminated in 2011 based on the observation that V710 was unlikely to demonstrate a statistically significant clinical benefit, and a safety concern regarding overall mortality and multi-organ dysfunction that occurred with greater frequency in vaccine recipients compared with placebo recipients [4].
Reference 5 discloses various S. aureus antigens and their combinations as vaccine strategics. Reference 6 discloses that S. aureus polypeptide antigens can be unstable in a simple buffer solution, and that antigens can be stabilised by the presence of a stabilizing additive, e.g. EDTA. Instability of the antigens is undesirable because (1) it does not allow vaccines to be stored for a long period of time before administration, and (2) inconsistency of vaccines from batch to batch can affect quality and regulatory approval requirements. Furthermore, manufacture of vaccines containing these unstable antigens can be complicated and involve multiple purification steps. Therefore it is an object of the invention to identify further strategies to stabilize S. aureus polypeptide antigens in immunogenic compositions.